Differential Regulation of Male-Hormones-Related Enhancers Revealed by Chromatin Accessibility and Transcriptional Profiles in Pig Liver.

Surgical castration can effectively avoid boar taint and improve pork quality by removing the synthesis of androstenone in the testis, thereby reducing its deposition in adipose tissue. The expression of genes involved in testis-derived hormone metabolism was altered following surgical castration, but the upstream regulatory factors and underlying mechanism remain unclear. In this study, we systematically profiled chromatin accessibility and transcriptional dynamics in liver tissue of castrated and intact full-sibling Yorkshire pigs. First, we identified 897 differentially expressed genes and 6864 differential accessible regions (DARs) using RNA- and ATAC-seq. By integrating the RNA- and ATAC-seq results, 227 genes were identified, and a significant positive correlation was revealed between differential gene expression and the ATAC-seq signal. We constructed a transcription factor regulatory network after motif analysis of DARs and identified a candidate transcription factor (TF) SP1 that targeted the HSD3B1 gene, which was responsible for the metabolism of androstenone. Subsequently, we annotated DARs by incorporating H3K27ac ChIP-seq data, marking 2234 typical enhancers and 245 super enhancers involved in the regulation of all testis-derived hormones. Among these, four typical enhancers associated with HSD3B1 were identified. Furthermore, an in-depth investigation was conducted on the androstenone-related enhancers, and an androstenone-related mutation was identified in a newfound candidatetypical enhancer (andEN) with dual-luciferase assays. These findings provide further insights into how enhancers function as links between phenotypic and non-coding area variations. The discovery of upstream TF and enhancers of HSD3B1 contributes to understanding the regulatory networks of androstenone metabolism and provides an important foundation for improving pork quality.

Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens.

BACKGROUND: Exploring the hypoxia adaptation mechanism of Tibetan chicken is of great significance for revealing the survival law of Tibetan chicken and plateau animal husbandry production. To investigate the hypoxia adaptation of Tibetan chickens (TBCs), an integrative metabolomic-transcriptomic analysis of the liver on day 18 of embryonic development was performed. Dwarf laying chickens (DLCs), a lowland breed, were used as a control. RESULTS: A total of 1,908 metabolites were identified in both TBCs and DLCs. Energy metabolism and amino acid metabolism related differentially regulated metabolites (DRMs) were significantly enriched under hypoxia. Important metabolic pathways including the TCA cycle and arginine and proline metabolism were screened; PCK1, SUCLA2, and CPS1 were found to be altered under hypoxic conditions. In addition, integrated analysis suggested potential differences in mitochondrial function, which may play a crucial role in the study of chicken oxygen adaptation. CONCLUSIONS: These results suggest that hypoxia changed the gene expression and metabolic patterns of embryonic liver of TBCs compared to DLCs. Our study provides a basis for uncovering the molecular regulation mechanisms of hypoxia adaptation in TBCs with the potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet plateau, and may even contribute to the study of diseases caused by hypoxia.

Varied hypoxia adaptation patterns of embryonic brain at different development stages between Tibetan and Dwarf laying chickens.

BACKGROUND: Tibetan chickens (Gallus gallus; TBCs), an indigenous breed distributed in the Qinghai-Tibet Plateau, are well adapted to the hypoxic environment. Currently, the molecular genetic basis of hypoxia adaptation in TBCs remains unclear. This study investigated hypoxia adaptation patterns of embryonic brain at different development stages by integrating analysis of the transcriptome with our previously published metabolome data in TBCs and Dwarf Laying Chickens (DLCs), a lowland chicken breed. RESULTS: During hypoxia, the results revealed that 1334, 578, and 417 differentially expressed genes (DEGs) (|log2 fold change|>1, p-value < 0.05) on days 8, 12, and 18 of development, respectively between TBCs and DLCs. Gene Ontology (GO) and pathway analyses revealed that DEGs are mainly related to metabolic pathways, vessel development, and immune response under hypoxia. This is consistent with our metabolome data that TBCs have higher energy metabolism than DLCs during hypoxia. Some vital DEGs between TBCs and DLCs, such as EPAS1, VEGFD, FBP1, FBLN5, LDHA, and IL-6 which are involved in the HIF pathway and hypoxia regulation. CONCLUSION: These results suggest varied adaptation patterns between TBCs and DLCs under hypoxia. Our study provides a basis for uncovering the molecular regulation mechanism of hypoxia adaptation in TBCs and a potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet Plateau, and may even contribute to the study of brain diseases caused by hypoxia.

Insight into adaption to hypoxia in Tibetan chicken embryonic brains using lipidomics.

Tibetan chickens (Gallus gallus; TBCs) are a good model for studying hypoxia-related challenges. However, lipid composition in TBC embryonic brains has not been elucidated. In this study, we characterized brain lipid profiles of embryonic day 18 TBCs and dwarf laying chickens (DLCs) during hypoxia (13% O2, HTBC18, and HDLC18) and normoxia (21% O2, NTBC18, and NDLC18) by using lipidomics. A total of 50 lipid classes, including 3540 lipid molecular species, were identified and grouped into glycerophospholipids, sphingolipids, glycerolipids, sterols, prenols, and fatty acyls. Of these lipids, 67 and 97 were expressed at different levels in the NTBC18 and NDLC18, and HTBC18 and HDLC18 samples, respectively. Several lipid species, including phosphatidylethanolamines (PEs), hexosylceramides, phosphatidylcholines (PCs), and phospha-tidylserines (PSs), were highly expressed in HTBC18. These results suggest that TBCs adapt bet-ter to hypoxia than DLCs and may have distinct cell membrane composition and nervous system development, at least partly owing to differential expression of several lipid species. One tri-glyceride, one PC, one PS, and three PE lipids were identified as potential markers that discrim-inated between lipid profiles of the HTBC18 and HDLC18 samples. The present study provides valuable information about the dynamic composition of lipids in TBCs that may explain the adaptation of this species to hypoxia.